How to diagnose heparin-induced thrombocytopenia (HIT) in a patient with a history of heparin use, thrombocytopenia, chronic kidney disease (CKD), diabetes, and congestive heart failure (CHF)?

Diagnosing Heparin-Induced Thrombocytopenia (HIT)

Use the 4Ts score to calculate clinical probability, then order anti-PF4 antibody testing immediately if the score is intermediate (4-5) or high (≥6), and discontinue all heparin while starting alternative anticoagulation without waiting for laboratory results. 1

Step 1: Calculate the 4Ts Score

The 4Ts score evaluates four components, each scored 0-2 points 1:

Thrombocytopenia Severity

• 2 points: Platelet fall >50% AND platelet nadir 20-100 × 10⁹/L (no recent surgery in past 3 days) 1
• 1 point: Platelet fall >50% but recent surgery within 3 days, OR platelet fall 30-50%, OR platelet nadir 10-19 × 10⁹/L 1
• 0 points: Platelet fall <30% OR platelet nadir <10 × 10⁹/L 1

Timing of Platelet Fall

• 2 points: Days 5-10 after heparin start (or ≤1 day if heparin exposure in previous 5-30 days) 1
• 1 point: Consistent with days 5-10 fall but unclear timing, OR >10 days, OR ≤1 day with heparin exposure 30-100 days prior 1
• 0 points: Platelet fall <4 days without recent heparin exposure (past 100 days) 1

Thrombosis or Other Sequelae

• 2 points: New confirmed thrombosis, skin necrosis, or acute systemic reaction after IV heparin bolus 1
• 1 point: Progressive or recurrent thrombosis, non-necrotizing skin lesions, or suspected thrombosis not yet proven 1
• 0 points: None 1

Other Causes of Thrombocytopenia

• 2 points: No other evident explanation for platelet fall 1
• 1 point: Possible other cause present 1
• 0 points: Definite other cause identified 1

Score Interpretation 1:

• 0-3 points: Low probability (0-3% HIT risk) - HIT excluded, continue heparin if needed
• 4-5 points: Intermediate probability - proceed with testing and treatment
• 6-8 points: High probability - proceed with testing and treatment

Step 2: Initial Laboratory and Imaging Workup

When HIT is suspected, immediately order 1:

• PT, aPTT, fibrinogen, D-dimers to exclude DIC (which can coexist with severe HIT) 1
• Doppler ultrasound of lower extremities (or upper extremities if central catheter present) to screen for thrombosis 1
• Verify thrombocytopenia by examining blood smear to exclude platelet clumping; repeat sample in citrate tube if EDTA-induced pseudothrombocytopenia suspected 1

Step 3: Anti-PF4 Antibody Testing

For intermediate or high probability (4Ts ≥4), order anti-PF4 antibody immunoassay immediately 1, 2:

Immunoassay Characteristics

• High sensitivity (excellent negative predictive value) - negative result effectively rules out HIT 1, 2, 3
• Lower specificity - antibodies present in up to 50% of cardiac surgery patients without clinical HIT 1
• Improved specificity when using IgG-specific assays with quantitative results (optical density values) 1

Result Interpretation

• Negative immunoassay: HIT excluded, no further testing needed 1, 4
• Positive immunoassay with high optical density: Proceed to functional assay for confirmation 1, 4

Step 4: Functional Assay for Confirmation

If immunoassay is positive with intermediate or high clinical probability, order a functional test 1:

Serotonin Release Assay (SRA) - Gold Standard

• Detects only platelet-activating antibodies capable of causing clinical HIT 2, 4, 5
• Sensitivity 97.2% with near 100% specificity 4, 5
• Limitations: Requires specialized laboratory, radioactive materials, and reactive donor platelets; results may take several days 2, 3

Alternative Functional Tests

• Heparin-Induced Platelet Activation (HIPA) test - rarely used in some countries 1
• Platelet aggregation tests (PAT) - less sensitive than SRA 1

Positive functional assay confirms HIT diagnosis 1, 4

Step 5: Immediate Management Actions

Do not wait for laboratory results before acting 1, 4:

For Intermediate or High Probability (4Ts ≥4)

1. Discontinue all heparin immediately (UFH and LMWH) 1, 4

2. Start alternative non-heparin anticoagulant at therapeutic dose 1, 6:

   • Argatroban (initial dose 2 mcg/kg/min, adjust to aPTT 1.5-3× baseline, max 10 mcg/kg/min) 7, 6
   • Danaparoid 5, 6
   • Fondaparinux 5, 6
   • Bivalirudin 6

3. Do NOT start warfarin until platelet count recovers to ≥150 × 10⁹/L 6

For Low Probability (4Ts ≤3)

• Continue heparin if clinically indicated 1
• No anti-PF4 antibody testing needed 1
• Search for alternative causes of thrombocytopenia 1

Special Considerations for Your Patient Population

Chronic Kidney Disease

• Argatroban is preferred as it is hepatically cleared, not renally eliminated 7, 8
• Dose adjustment based on aPTT monitoring, not renal function 7, 8
• Can be used during hemodialysis sessions 8

Post-Cardiac Surgery Context

• 4Ts score is less reliable after cardiac surgery due to multiple confounding factors 1
• Look for "biphasic" platelet pattern: initial postoperative recovery followed by secondary drop - highly predictive of HIT 1
• Anti-PF4 antibodies present in ~50% of cardiac surgery patients without clinical HIT, reducing positive predictive value of immunoassays 1

Common Pitfalls to Avoid

• Do not delay heparin cessation waiting for laboratory confirmation - thrombosis risk is ~5% per day without treatment 4
• Do not start warfarin early - can cause venous limb gangrene; wait until platelets ≥150 × 10⁹/L, then use low doses (≤5 mg warfarin) with ≥5 days overlap with alternative anticoagulant 6
• Do not rely on immunoassay alone - 24-61% of patients with high 4Ts scores and positive ELISA do not have HIT 4, 5
• Do not use LMWH as alternative - high cross-reactivity with HIT antibodies 1, 6
• Remember HIT can occur with heparin flushes alone or isolated hemodialysis use 8